Adolescent idiopathic scoliosis (AIS) is a leading cause of pediatric structural spinal deformity, impacting up to 3-4% of adolescents globally. The lack of unifying mechanisms to explain its development and paucity of suitable animal or in-vitro study models have made it difficult to institute effective therapeutic approaches for AIS. Paraspinal muscles are crucial structures for mobility and stability of the spine, but their role in AIS is not clearly understood. Phenotypically, paraspinal muscle in AIS display myopathic features including fibrosis and fatty involution. However, the mechanism of development of paraspinal muscle phenotype and its contribution in AIS pathogenesis is not elucidated. This project aimed to understand the development of paraspinal muscle phenotype in patients with AIS via characterization of inflammatory phenotype, fibrosis and fatty involution, and autophagic machinery in paraspinal muscle. We demonstrated the presence of paraspinal muscle fibrosis and fatty involution on both concave and convex sides of the scoliotic curve. The potential crosstalk between TGF- family and mesenchymal progenitors expressing PDGFR- was identified and represent the crucial mechanism associated with development of muscle phenotype in AIS. We also demonstrated the upregulation of canonical TGF/Smad signaling pathways and Smad independent non-canonical TGFsignaling pathways including p38 and JNK (p46/54) MAPKs in paraspinal muscle on the concave versus convex side which may be associated with an enhanced fibrosis and fatty involution on the concave side in comparison to the convex side. Furthermore, the data suggest differential autophagy activation in paraspinal muscle in AIS with convex side demonstrating enhanced expression of autophagy markers in comparison to the concave side. The data also demonstrate that the Akt dependent inhibition of FoxO3A transcription factor could potentially lead to the suppression of expression of autophagy markers on the concave side in comparison to the convex side. The upregulation of fibrogenic and adipogenic pathways and suppression of expression of autophagy markers may associate with a more severe phenotype in paraspinal muscle on the concave side in comparison to the convex side. The assessment of muscle health in AIS opens therapeutic entry points to influence muscle phenotype in AIS which may impact the patient outcomes. / Thesis / Doctor of Philosophy (Medical Science)

Abstract The first part of this research was focused on the relationship between injury severity and cell death mechanisms after spinal cord ischemia-reperfusion injury. The major blood supply to the thoracolumbar spinal cord comes from the segmental arteries originating from the thoracoabdominal aorta. Paraplegia cause by spinal cord ischemia is a devastating complication of thoracoabdominal aortic surgery. Previous studies indicated that ischemia-reperfusion injury of the central nervous system causes two distinct types of cell death, necrosis and apoptosis. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. In the first series of our experiments, by occluding the descending thoracic aorta with or without simultaneously inducing hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia-reperfusion (SCIR) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, SCIR resulted in minor tissue destruction associated with persistently abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of ischemia-reperfusion (I/R) injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlated with neurological performance. These findings implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention. Based on the knowledge that bPrevious studies have implicated both excitotoxicity and apoptosis are involved in the pathogenesis of SCIR injury, we proposedtested the possibility that the N-methyl-D-aspartate (NMDA) receptor antagonist (dizocilpine maleate: (MK801) and the protein synthesis inhibitor (cycloheximide) would produce a synergic effect in the treatment of SCIR injury. In the second series of experiments, I/R iSpinal cord ischemia-reperfusion injury was induced by a thoracic aortic occlusion and blood volume reduction, followed by reperfusion and volume restoration. ischemia-reperfusion Rats were treated with vehicle, MK801, cycloheximide, or combination of MK801 and cycloheximide in combination. The MK801 and combined therapy group got a better recovery of hHind limb motor function recovery was better in the MK801 and combined-therapy groups than in the control and cycloheximide groups. On the 7th day after ischemia-reperfusion injury, all three treated groups showed significantly higher neuronal survival rates (NSR) than that of the control group. Among the three treated groups, the combined-treatment group showed the highest NSR. In addition, the Ttherapeutic effect of the combined-treatment group (27.4% increase of NSR) iwas better than the anticipated by the addition of MK801 and cycloheximide based on NSR data group. The number of apoptotic cells of was significantly reduced in the cycloheximide group and the combined-treatment group, as compared to that of the control group. It was unchanged in the MK-801 group. These results suggest that combined treatments directed at blocking both NMDA receptor-mediated excitotoxic necrosis and caspase-mediated apoptosis might have synergic therapeutic potential in reducing SCIR injury. Mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinases (JNK), p38, and extracellular signal-regulated kinases (ERK), play important roles in the transduction of stressful signals and the integration of cellular responses. Although it has been generally held that the JNK and p38 pathways are related to cell death and degeneration, while the ERK pathway, cell proliferation and survival, controversy still exists. The roles of the ERK pathway in I/R injury of the CNS, in particular, remain to be clarified, because contradictory data have been reported by different investigators. Given this controversy, in the third series of experiments, we examined in injured spinal cords the temporal and spatial profiles of ERK1/2 activation following SCIR, and the effects of inhibiting the kinase that phosphorylates ERK1/2, MEK. The results showed that I/R injury induced an immediate phosphorylation of ERK1/2 in the spinal cord, which was alleviated by a MEK inhibitor, U0126. The control group was characterized by poorer neurological outcome, more severe tissue destruction, pronounced apoptosis, and lower neuronal survival. In contrast, the U0126-treated group demonstrated more apparent improvement of hind limb motor function, less tissue destruction, lack of apoptosis, and higher neuronal survival. In addition, administration of U0126 also significantly increased the activation of nuclear factor-£eB (NF-£eB) and the expression of cellular inhibitor of apoptosis protein 2 (c-IAP2). These findings implicate that the mechanisms underlying the neuroprotection afforded by ERK1/2 inhibition may be through the NF-£eB-c-IAP2 axis. The activation of the MEK-ERK signaling pathway appeared to be harmful in SCIR injury. Strategies aimed at blocking this pathway may bear potential therapeutic benefits in the treatment of SCIR injury. The second part of the research was focused on the pathophysiology of surgery-associated paraspinal muscle injury and measures to protect surgically violated paraspinal muscles. The wide dissection and forceful retraction of paraspinal muscles which are often required for posterior spinal sugery may severely jeopardize the muscles structurally and functionally. Immediate posteoperative pathological changes in the surgically violated paraspinal muscles may cause severe pain and a delay of patient ambulation. Long-term sequelae of surgical injury of paraspinal muscles include chronic back pain and impaired back muscle strength. Ironically, being a common complication of posterior spinal surgery, paraspinal muscle injury is so often neglected. Limited previous data indicate that the underlying pathophysiology of muscle damage involve both mechanical and ischemic mechanisms. We hypothesized that surgical dissection and retraction may produce oxidative stress within the paraspinal muscles. Meanwhile, we also proposed that the oxidative stress may trigger certain protective mechanisms within the insulted muscles. The first part of our study was a human study conducted to assess the significance of oxidative stress, and the relationship between it and the stress response mediated by heat shock protein 70 (HSP70) induction within paraspinal muscles under intraoperative retraction. A group of patients with lumbar spondylolisthesis treated with posterolateral lumbar spinal fusion, pedicle fixation and laminectomy were enrolled. Multifidus muscle specimens were harvested intraoperatively before, at designated time points during, and after surgical retraction. Muscle samples were analyzed for HSP70 and malondialdehyde (MDA) levels. Both HSP70 expression and MDA production within multifidus muscle cells were increased significantly by retraction. HSP70 expression then dropped after a peak at 1.5 hr of retraction, whereas MDA levels remained elevated even after release of retractors for reperfusion of the muscles. Histopathological and immunohistochemical evidence indicated that the decline of HSP70 synthesis within muscle cells after prolonged retraction was the result of severe muscle damage. These results highlighted the noxious impact of intraoperative retraction on human paraspinal muscles, and the significance of oxidative stress at the cellular and molecular levels. It is also implicated that intraoperative maneuvers aimed at reducing the oxidative stress within the paraspinal muscles may help attenuating surgery-associated paraspinal muscle damage. Given the findings of the first part of our study, and the knowledge that inflammation is a major postoperative pathological finding in surgically injured paraspinal muscles, we proceeded to examine the roles of two important inflammatory mediators, cyclooxygenase (COX)-2 and nuclear factor (NF)-£eB, in the pathogenesis of retraction-associated paraspinal muscle injury. A rat model of paraspinal muscle dissection and retraction that mimicks the conditions in human posterior spinal surgery was established. In the control group, paraspinal muscles were dissected from the spine through a dorsal incision, and then laterally retracted. Paraspinal muscle specimens were harvested before, and at designated time points during and after persistent retraction. The time course of NF-£eB activation as well as the expression of COX-2 were examined. Severity of inflammation was evaluated based on histopathology and myeloperoxidase (MPO) activity. NF-£eB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. In the control group, retraction induced an early increase of NF-£eB/DNA binding activity in paraspinal muscle cells, which persited throughout the whole course of retraction. COX-2 expression was not detectable until 1 day after surgery, and reached a peak at 3 days. The time course of COX-2 expression correlated with that of inflammatory pathology and MPO activity. Extensive muscle fiber loss and collagen fiber replacement were observed at 7 days after surgery. Pretreatment with PDTC inhibited intraoperative NF-£eB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Fibrosis following inflammation was also significantly abolished by PDTC administration. These findings indicate that NF-£eB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. Therapeutic strategies involving NF-£eB inhibition may be applicable to the prevention of such injury.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第19643号 / 人健博第35号 / 新制||人健||3(附属図書館) / 32679 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 坪山 直生, 教授 山田 重人, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

As últimas estimativas da Organização Mundial da Saúde mostram a ocorrência de 14,1 milhões de novos casos de câncer em 2012. Sendo que desses casos, 8,2 milhões virão a óbito. Os tumores paravertebrais e intracraniais, também chamados de cânceres do Sistema Nervoso Central, tem origem no cérebro, nervos cranianos e meninges. Uma nova modalidade de braquiterapia começou a ser usada nesta última década. Neste procedimento, placas poliméricas flexíveis, carregando fósforo-32, são colocadas próximas ou em contato ao tumor para o tratamento. Este tratamento apresenta vantagens em relação aos demais porque aplica uma alta taxa de dose no tumor poupando tecidos sadios. A produção destas placas ainda é pouco estudada, embora já existam resultados satisfatórios no seu uso para o tratamento dos cânceres do sistema nervoso central. Neste trabalho foram realizados estudos iniciais para a produção deste tipo de placas poliméricas para braquiterapia. Foram avaliadas as propriedades mecânicas e a capacidade de imobilização de material radioativo de duas resinas comercias, uma poliuretânica e outra epoxídica, com e sem presença de substrato de policarbonato. Os testes iniciais apontaram o uso da resina epoxídica como melhor alternativa e com o uso dela foram feitos os primeiros protótipos e testes. O uso do policarbonato como substrato não foi necessário em uma das metodologias, facilitando o procedimento, mas oferecendo uma barreira menor de segurança. Os ensaios de tração mostraram que a adição de solução ácida à resina epóxi alterou suas características mecânicas, mas houve uma pequena melhora em sua flexibilidade. Os testes de adesão evidenciaram uma melhor adesão da resina à face texturizada do policarbonato. A termogravimetria mostrou que a solução ácida adicionada a resina fica presa à estrutura mesmo com elevações de temperatura acima de 100°C. A resina epoxídica utilizada teve a capacidade de incorporar o material radioativo em forma de solução ácida e manter-se estanque após testes de esfregaço e imersão em líquido quente. De acordo com os resultados obtidos, a produção destas placas com resina epoxídica é possível e atende às normas internacionais de segurança contra vazamento de material radioativo para fontes utilizadas em braquiterapia. / The latest estimates of the World Health Organization show the occurrence of 14.1 million new cases of cancer in 2012. From these cases, 8.2 million will come to death. The paraspinal and intracranial tumors, also called central nervous system cancers, are originated in the brain, cranial nerves and meninges. A new brachytherapy modality began to be used in the last decade. In this procedure, flexible, polymeric plaques carrying phosphorus-32 are placed in contact or close to the tumor for treatment. This treatment has advantages over others because it applies a high dose rate in the tumor sparing healthy tissues. The production of these plaques is not well known, although there are satisfactory results in its use for the treatment of central nervous system cancers. This work carried out initial studies for the production of this type of polymer plaques for brachytherapy. The mechanical properties and immobilization capacity of radioactive material, from two commercial resins, epoxy and polyurethane, with or without the presence of polycarbonate as substrate were evaluated. Initial tests showed the use epoxy resin as the best alternative and the first prototypes and tests with use of it were made. The use of polycarbonate as a substrate was not required on one of the methodologies, facilitating the procedure but offering a lower security barrier. The tensile tests showed that addition of acid to the epoxy resin solution changed its mechanical properties, but there was a small improvement in flexibility. Adhesion tests showed better adhesion of the resin to the textured surface of the polycarbonate. The thermogravimetric analysis showed that the acid solution added to the resin structure is sealed even with temperature rises above 100°C. The epoxy resin used has the ability to incorporate the radioactive material in the form of acid solution and remain tight after wiping and immersion in hot liquid tests. According to the results, the production of these plaques with epoxy resin is possible and meets international safety standards for leakage of radioactive material in radioactive sources used in brachytherapy.

As últimas estimativas da Organização Mundial da Saúde mostram a ocorrência de 14,1 milhões de novos casos de câncer em 2012. Sendo que desses casos, 8,2 milhões virão a óbito. Os tumores paravertebrais e intracraniais, também chamados de cânceres do Sistema Nervoso Central, tem origem no cérebro, nervos cranianos e meninges. Uma nova modalidade de braquiterapia começou a ser usada nesta última década. Neste procedimento, placas poliméricas flexíveis, carregando fósforo-32, são colocadas próximas ou em contato ao tumor para o tratamento. Este tratamento apresenta vantagens em relação aos demais porque aplica uma alta taxa de dose no tumor poupando tecidos sadios. A produção destas placas ainda é pouco estudada, embora já existam resultados satisfatórios no seu uso para o tratamento dos cânceres do sistema nervoso central. Neste trabalho foram realizados estudos iniciais para a produção deste tipo de placas poliméricas para braquiterapia. Foram avaliadas as propriedades mecânicas e a capacidade de imobilização de material radioativo de duas resinas comercias, uma poliuretânica e outra epoxídica, com e sem presença de substrato de policarbonato. Os testes iniciais apontaram o uso da resina epoxídica como melhor alternativa e com o uso dela foram feitos os primeiros protótipos e testes. O uso do policarbonato como substrato não foi necessário em uma das metodologias, facilitando o procedimento, mas oferecendo uma barreira menor de segurança. Os ensaios de tração mostraram que a adição de solução ácida à resina epóxi alterou suas características mecânicas, mas houve uma pequena melhora em sua flexibilidade. Os testes de adesão evidenciaram uma melhor adesão da resina à face texturizada do policarbonato. A termogravimetria mostrou que a solução ácida adicionada a resina fica presa à estrutura mesmo com elevações de temperatura acima de 100°C. A resina epoxídica utilizada teve a capacidade de incorporar o material radioativo em forma de solução ácida e manter-se estanque após testes de esfregaço e imersão em líquido quente. De acordo com os resultados obtidos, a produção destas placas com resina epoxídica é possível e atende às normas internacionais de segurança contra vazamento de material radioativo para fontes utilizadas em braquiterapia. / The latest estimates of the World Health Organization show the occurrence of 14.1 million new cases of cancer in 2012. From these cases, 8.2 million will come to death. The paraspinal and intracranial tumors, also called central nervous system cancers, are originated in the brain, cranial nerves and meninges. A new brachytherapy modality began to be used in the last decade. In this procedure, flexible, polymeric plaques carrying phosphorus-32 are placed in contact or close to the tumor for treatment. This treatment has advantages over others because it applies a high dose rate in the tumor sparing healthy tissues. The production of these plaques is not well known, although there are satisfactory results in its use for the treatment of central nervous system cancers. This work carried out initial studies for the production of this type of polymer plaques for brachytherapy. The mechanical properties and immobilization capacity of radioactive material, from two commercial resins, epoxy and polyurethane, with or without the presence of polycarbonate as substrate were evaluated. Initial tests showed the use epoxy resin as the best alternative and the first prototypes and tests with use of it were made. The use of polycarbonate as a substrate was not required on one of the methodologies, facilitating the procedure but offering a lower security barrier. The tensile tests showed that addition of acid to the epoxy resin solution changed its mechanical properties, but there was a small improvement in flexibility. Adhesion tests showed better adhesion of the resin to the textured surface of the polycarbonate. The thermogravimetric analysis showed that the acid solution added to the resin structure is sealed even with temperature rises above 100°C. The epoxy resin used has the ability to incorporate the radioactive material in the form of acid solution and remain tight after wiping and immersion in hot liquid tests. According to the results, the production of these plaques with epoxy resin is possible and meets international safety standards for leakage of radioactive material in radioactive sources used in brachytherapy.

Intensity modulated arc therapy is a novel treatment technique that has shown great potential to be superior to conventional intensity modulated radiotherapy, both in terms of treatment plan quality as well as treatment delivery. Based on previous literature, a simplified technique called two-step intensity modulated arc therapy (2-step IMAT) was implemented into a treatment planning system. In order to automatically generate treatment plans for this technique, a beam portal shaping method was developed to generate beam segments. A sensitivity analysis was carried out on a geometric phantom to determine optimal parameters for the 2-step IMAT implementation for that particular phantom. The segment weights were optimized using the dose-based and dose-volume-based objective functions. The optimal solution search was based on the gradient-descend algorithm. The dose-based objective function was implemented using a so-called lambda-value-dose-based objective function developed in this work in order to increase both speed and flexibility of the optimization. The successful implementation demonstrated the feasibility of automatic 2-step IMAT treatment planning. A comparison of conventional arc therapy and 2-step IMAT showed improvements in the target dose uniformity by about 50% for both geometric phantom and clinical paraspinal tumor case, whilst also improving the organ sparing. The comparisons between the lambda-value-dose-based and dose-volume-based optimizations showed a speed advantage of the former by a factor of over five in the phantom study. The current beam portal shaping approach can be improved by optimizing the segment width and including multiple organs-at-risk in the segment generation algorithm. Future work will also include the implementation of a stochastic optimization to minimize the chance of getting trapped in local minima during the segment weight optimization. In summary, the work of this research showed that the automatic 2-step IMAT planning is a viable technique that can result in highly conformal plans while keeping the treatment planning and delivery simple and straightforward.

Le rachis lombaire est à la fois capable de répondre à des exigences de stabilité pour protéger les structures neurologiques ou ostéo-ligamentaires et de mouvement pour assumer les gestes de la vie quotidienne, professionnelle et sportive. La lombalgie, pathologie multifactorielle, s'accompagne de perturbations musculaires, réflexes ou comportementales. La complexité de ces adaptations explique pourquoi il est encore difficile de savoir comment un sujet devient lombalgique ou pourquoi il le reste. Ce travail de recherche s'est focalisé sur l'étude de certaines adaptations du rachis lombaire en situation aiguës ou chroniques. Les objectifs étaient d'analyser l'influence (i) des tissus de soutien sur le comportement musculaire lombaire (ii) du gainage abdominal sur l'efficience des membres inférieurs, (iii) de la fatigue des érecteurs spinaux sur la réponse réflexe chez le sujet sain et (iv) d'un programme de rééducation chez le lombalgique. Les résultats obtenus soulignent le rôle central de l'effecteur neuromusculaire lombaire. Le maintien de certaines postures entraîne des adaptations mécaniques (pression intramusculaire) et métaboliques (oxygénation musculaire) limitant l'efficience des érecteurs spinaux. Le renforcement abdominal, probablement par son action stabilisatrice lombaire, modifie la raideur du système tronc -membres inférieurs et peut-être l'aptitude au saut vertical. Une fatigue lombaire induite provoque une adaptation réflexe chez le sujet sain (gain d'amplitude et peut-être de latence) pour compenser la perte de force. Enfin, un programme de restauration fonctionnelle permettrait, chez le lombalgique chronique, de modifier les capacités d'anticipation en limitant les activations musculaires exagérées et la réponse réflexe à une perturbation, évoquant l'émergence de nouvelles stratégies d'adaptation. Ce travail suggère la possibilité de nouvelles approches dans un cadre sportif ou médical. / The lumbar spine is able to meet both stability requirements for protecting neurological and osteoligamentous spine structures and movement requirements for performing professional, sports, and daily life activities. Low back pain, a multi-factorial disease, is associated with abnormal muscle function, neuromuscular alterations, and adverse behavioural reactions. The complexity and the variability of all these changes explain why the exact cause of back pain remains unknown. This thesis focused on the study of the lumbar spine adaptations in various acute or chronic situations. The goal was to explore (i) the influence of posture and passive contributions on paraspinal muscle pressure and oxygenation adaptations, (ii) the consequences of abdominal reinforcement on trunk and leg stiffness, (iii) the effects of induced paraspinal fatigue or (iv) rehabilitation programs on reflex modulation in healthy subjects and chronic low back pain patients, respectively. The results emphasize the central role of the neuromuscular lumbar effector. Maintaining certain postures causes mechanical and oxygenation paraspinal muscular changes that may explain passive limitations on paraspinal muscle efficiency; the modifications induced by abdominal training in healthy subjects suggest a possible role of the spine on trunk and leg stiffness changes; a paraspinal muscle fatigue paradigm illustrates the reflex modulation which compensates a loss of force; finally, a functional restoration program designed for chronic low back pain disorders targets neuromuscular behaviour changes via modulation of the trunk reflex response, thus advocating a possible way to increase the range of control strategies. This work opens the door for new therapeutic strategies.

La connaissance de l’anatomie des muscles paravertébraux lombaires et la compréhension de leur mode d’action représentent un enjeu majeur de la prise en charge des lombalgies. L’expérience chirurgicale montre que les muscles paravertébraux constituent une volumineuse masse musculaire dépourvue de gros tendons et engainée dans un fascia inextensible. En biomécanique, la force maximale d’un muscle est positivement corrélée à la surface de section des tendons et du corps charnu. Il existe probablement, au niveau lombaire, une étonnante discordance entre le volume musculaire, qui suggère une force élevé, et celui des tendons dont la résistance mécanique est très limitée. Les modèles biomécaniques classiques semblent inappropriées pour décrire le mode d’action des muscles paravertébraux. Selon certains modèles biomécaniques dérivés de la théorie des poutres, l’augmentation de la dureté ou élasticité au sein du compartiment paravertébral serait le mécanisme principal de la stabilisation de la colonne vertébrale.Ces travaux se sont articulés autour de deux grands axes. L’axe anatomique avait pour objectif de vérifier l’hypothèse de la discordance morphologique tendon/muscle des principaux muscles paravertébraux lombaires. L’axe radiologique avait pour objectif la mise en place de protocoles d’élastographie par résonance magnétique et ultrasonore pour l’exploration de l’élasticité des différents muscles paravertébraux lombaires au repos et dans plusieurs postures différentes.Les résultats des travaux anatomiques montrent un ratio de surface tendon/muscle du multifudus et de l’iliocostalis extrêmement bas et une petite surface de section du multifidus suggérant que muscles ne sont pas capables de générer l’extension dorsale de la colonne lors de la contraction musculaire. Ils semblent plutôt stabiliser la colonne vertébrale en lui assurant une certaine rigidité assurée par un volume musculaire conséquent confiné dans une loge inextensible. Au moyen de l’élastographie, nous montrons que l’élasticité des muscles paravertébraux est la plus basse au repos, en décubitus et qu’elle n’est pas influencée par la flexion ou l’extension passive de la colonne, ni par l’étirement du fascia thoracolombaire. L’élasticité augmente lors des positions : assise, debout, penchée en avant et en arrière. Le comportement biomécanique de chaque muscle est différent selon les postures. Ces travaux confirment qu’il existe des modifications significatives de l’élasticité lors de la mise en charge de la colonne. Les lombalgies sont associées à des modifications d’élasticité de la colonne et des muscles paravertébraux observées lors de l’examen clinique, l’élastographie pourrait permettre de les explorer et de les caractériser de façon objective et non invasive. / Knowledge about the anatomy and the mode of action of the lumbar paraspinal muscles is major importance for the management of low back pain. Surgical experience shows that the paraspinal muscles constitute a voluminous muscle mass without large tendons and enclosed in an inextensible fascia. In biomechanics, the maximum strength of a muscle is positively correlated to the cross-sectional area of tendons and the muscle belly. Therefore, there is a paradox between the presumed high strength of the voluminous muscle belly and the low strength of the tendons. Traditional biomechanical models seem inappropriate for describing the mode of action of the paraspinal muscles. According to the beam theory, increasing elasticity within the paraspinal compartment would allow the stabilization of the spine.The work has two broad objectives. The first objective was to assess the assumption that there is an inconsistency betwenn the cross-sectional area of the tendon and of the belly of the main paraspinal muscles, i.e. the multifidus, the longissius and the iliocostalis. The second objective was to establish elastography protocols with magnetic resonance imaging and ultrasonography for the exploration of the elasticity of the paraspinal muscles at rest and in several different postures. Results of the anatomical studies show that the tendon-to-muscle area ratios of the longissimis and the iliocostalis were extremely small, as well as cross-sectional area of the belly of the multifidus. That suggests that paraspinal muscles are not able to provide the dorsal extension of the spine during muscle contraction. Rather, they seem to stabilize the spine by providing it with a certain rigidity ensured by a substantial muscle volume contained in an inextensible compartment. Through elastography, we have shown that the elasticity of the paraspinal muscles was the lowest at rest, in decubitus. Elasticity was not influenced by passive flexion or extension of the spine, nor by the stretching of the thoracolumbar fascia. Elasticity increased during sitting, standing, bending forward and bending backward the compared to decubitus. The biomechanical behaviour of the longissimus, the iliocostalis and multifidus differed according to the postures. This work confirms that there are significant changes in elasticity during standing postures. Low back pain is associated with stiffness changes of the spine and of the paraspinal muscles that have been observed through clinical examination. In the future, elastography could allow exploring low back pain.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Department of Chiropractic, Durban University of Technology, Durban, South Africa, 2015. / Background: Spinal manipulative therapy (SMT) is a commonly used treatment for many musculoskeletal conditions although the exact mechanism explaining its effectiveness is not well understood. Several studies have investigated the effect of SMT on the paraspinal muscles where neuromuscular effects have been observed, however few studies have assessed whether these changes result in a change in the functioning of the paraspinal muscles. This study aimed to determine the effect of lower thoracic spinal manipulation compared to a placebo intervention on lumbar extensor muscle endurance in asymptomatic participants. Methodology: This was a quantitative, pre-test post-test, placebo controlled trial involving 40 male participants between the ages of 20 and 40 years. The participants were randomly allocated to either the lower thoracic spinal manipulation group or a placebo group. Manipulation was delivered using the Impulse Adjusting Instrument®. Objective measures included lumbar spinal range of motion, a paraspinal muscle endurance test, and surface electromyography readings. Subjective measures were the verbalisation of pain and/or discomfort during the paraspinal muscle endurance test. IBM® SPSS® statistics version 21 and STATA 11 were used to analyse the data. A p-value of <0.05 was considered statistically significant. Results: There were no statistically significant differences between the groups in terms of subjective and objective measurements. A trend of treatment effect was observed for paraspinal muscle endurance where the intervention group showed noticeable improvements in endurance scores. Conclusion: Further studies need to be conducted to determine if the trends observed would occur in a larger study population.

The aim of this thesis is to determine whether surface electromyography (EMG) can be used as a diagnostic tool in chiropractic practice to identify the functional status of the lumbar paraspinal muscles. There were two main studies to achieve this aim. The reliability and validity of the surface EMG signal to measure the activity of paraspinal muscles during maintenance of simple static postures was evaluated. During maintenance of static postures, the raw surface EMG signal was often contaminated by an electrocardiographic (ECG) signal. Although the ECG artefact was successfully removed using two different ECG removal techniques (manual and semi-automatic), the reliability of the surface EMG signal was not significantly improved (ICC less than 0.75) for both non-normalised and normalised data. Therefore the static postures that were used in this thesis did not provide a protocol that can be used to measure the functional status of the lumbar paraspinal muscles in clinical practice. However, when muscle contraction was at a moderate level, the reliability of EMG signal became better. Walking was considered to be a possible protocol to record a reliable surface EMG signal from paraspinal muscles. Three components of the surface EMG signal were used to characterise the pattern of muscle activity during steady state walking. The narrow window technique was used to characterise the peak activation point of the activity envelope in order to capture a stationary signal from which to calculate amplitude and frequency measures. Walking is a cyclic activity. The back muscles contract rhythmically during a single gait cycle. It is possible to identify the start and end points of the activity envelope associated with the rhythmic contraction of the muscles and define the timing of the muscle activation cycle relative to heel strike. The metronome was found to be useful to control the pace of natural walking in this study. The surface EMG signal of the first recording minute (1 ~ 2 minute) was not associated with a signal that was stable in terms of the parameters that were used in this study. It wa s found that the last recording minute (9 ~ 10 minute) can be used. This suggests that it may be necessary for subjects to walk for a defined period lasting some minutes before the commencement of recording of the surface EMG. Surface EMG may be used as a tool to measure activation patterns of the low back muscles during muscle contraction associated with the support of various static postures or during the execution of dynamic movements such as walking in the real world. The static postures used in this thesis to record the surface EMG signal from the lumbar paraspinal muscles were found not to provide the basis for a reliable and valid tool. However, a walking exercise might be an alternative activity which can be used easily in clinical practice. The components of the surface EMG signal that may be used in future studies might include measures of the amplitude, frequency and timing of the surface EMG signal.